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001-es BibID:	BIBFORM070808
Első szerző:	Murnyák Balázs (molekuláris biológus, genetikus)
Cím:	Genomic signature of PARP1 in glioblastoma molecular subtypes / Balázs Murnyák, Mahan C. Kouhsari, Rotem Hershkovitch, Álmos Klekner, Tibor Hortobágyi
Dátum:	2017
Megjegyzések:	Introduction: Glioblastoma (GBM) is an aggressive and frequent primary brain tumour in adults. Overexpression of PARP1 has been reported in various cancers, including GBM. Although PARP1 inhibition is a promising therapeutic target, no comprehensive analysis has addressed PARP1's expression regarding molecularheterogeneity in GBM.Aim of the study: The main objective of our study was to evaluate PARP1's associations with GBM lineage specific markers, and its transcriptomic subtypes.Material and methods: PARP1's somatic mutations, copy number alterations (CNAs), and mRNA expression, as well as survival data were collected from the ♭Glioblastoma Multiforme' TCGA dataset. A bioinformatic analysis was conducted a to evaluate PARP1's genetic signature, and prognostic role in GBM.Results: Our study revealed that PARP1 CNA gain and high mRNA expression level is a characteristic of Proneural (PN) and Classical (CL) GBM subtypes. Increased PARP1 levels exhibited an inverse correlation with patient survival (p<0.005) in the CL subgroup. ATRX (p=0.006), and TP53 (p=0.015) mutations were associated with increased PARP1 mRNA expression.Conclusions: Our study supports the therapeutic role of PARP inhibitors in GBM with the caveat that molecular heterogeneity needs to be taken into account.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok előadáskivonat Bioinformatics Oncogenetics PARP1 GBM
Megjelenés:	13th Warsaw International Medical Congress : Abstract Book / The Students' Scientific Association of the Medical University of Warsaw. - Warsaw : Medical University of Warsaw, 2017. - 242. p. -
További szerzők:	Kouhsari, Mahan C. Hershkovitch, Rotem Klekner Álmos (1970-) (idegsebész) Hortobágyi Tibor (1965-) (patológus)
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM070807
Első szerző:	Murnyák Balázs (molekuláris biológus, genetikus)
Cím:	Genomic signature of PARP1 in glioblastoma subtypes / Balázs Murnyák, Mahan C. Kouhsari, Rotem Hershkovitch, Tibor Hortobágyi
Dátum:	2017
Megjegyzések:	Glioblastoma (GBM) is a highly aggressive and the most prevalent primary brain tumour in adults. Despite extensive efforts to improve treatment, GBM is still resistant to current postoperative therapies making GBM a compelling field of cancer research. Overexpression of PARP1 has been reported in various cancers, including GBM. Although PARP1 inhibition is a promising therapeutic target, no comprehensive analysis has addressed PARP1's expression regarding molecular heterogeneity in GBM. The main objective of our study was to evaluate PARP1's associations with GBM lineage specific markers, and its transcriptomic subtypes. PARP1's somatic mutations, copy number alterations (CNAs), and mRNA expression, as well as survival data were collected from the ♭Glioblastoma Multiforme' TCGA dataset. A bioinformatic analysis was conducted to evaluate PARP1's genetic signature and prognostic role in GBM. Our study revealed that PARP1 CNA gain and high mRNA expression levels are characteristics of Proneural and Classical GBM subtypes. Increased PARP1 levels exhibited an inverse correlation with patient survival (p<0.005) in the Classical subgroup. ATRX (p=0.006), and TP53 (p=0.015) mutations were associated with increased PARP1 mRNA expression. The observed subtype-specificity suggests that PARP1, together with p53, could be not only a diagnostic marker to differentiate Proneural and Classical subtypes, but also a predictive marker of shorter survival and poor therapy response in the Classical subgroup. Our study supports the therapeutic role of PARP inhibitors in GBM with the caveat that molecular heterogeneity needs to be taken into account.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok előadáskivonat PARP1 GBM Bioinformatics
Megjelenés:	Translational Bioinformatics : Abstract Book / Wellcome Genome Campus. - P18. p.
További szerzők:	Kouhsari, Mahan C. Hershkovitch, Rotem Hortobágyi Tibor (1965-) (patológus)
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM068928
Első szerző:	Murnyák Balázs (molekuláris biológus, genetikus)
Cím:	PARP1 expression and its correlation with survival is tumour molecular subtype dependent in glioblastoma / Balázs Murnyák, Mahan C. Kouhsari, Rotem Hershkovitch, Bernadette Kálmán, György Marko-Varga, Álmos Klekner, Tibor Hortobágyi
Dátum:	2017
ISSN:	1949-2553
Megjegyzések:	Overexpression of PARP1 exists in various cancers, including glioblastoma (GBM). Although PARP1 inhibition is a promising therapeutic target, no comprehensive study has addressed PARP1's expression characteristics and prognostic role regarding molecular heterogeneity in astrocytomas including GBM. Our aim was to evaluate PARP1's associations with survival, WHO grade, lineage specific markers, and GBM transcriptomic subtypes. We collected genomic and clinical data from the latest glioma datasets of The Cancer Genome Atlas and performed PARP1, ATRX, IDH1, and p53 immunohistochemistry on GBM tissue samples. We demonstrated that PARP1 gain and increased mRNA expression are characteristics of high-grade astrocytomas, particularly of Proneural and Classical GBM subtypes. Additionally, higher PARP1 levels exhibited an inverse correlation with patient survival (p<0.005) in the Classical subgroup. ATRX (p=0.006), and TP53 (p=0.015) mutations were associated with increased PARP1 expression and PARP1 protein level correlated with ATRX loss and p53 overexpression. Furthermore, higher PARP1 expression together with wildtype TP53 indicated shorter survival (p=0.039). Therefore, due to subtype specificity, PARP1 expression level and TP53 mutation status are reliable marker candidates to distinguish Proneural and Classical subtypes, with prognostic and therapeutic implications in GBM.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban glioma glioblastoma p53 PARP1
Megjelenés:	Oncotarget. - 8 : 28 (2017), p. 46348-46362. -
További szerzők:	Kouhsari, Mahan C. Hershkovitch, Rotem Kálmán Bernadette Marko-Varga György Klekner Álmos (1970-) (idegsebész) Hortobágyi Tibor (1965-) (patológus)
Pályázati támogatás:	ÚNKP-16-3 Egyéb KTIA_13_NAP-A-II/7 Egyéb KTIA_13_NAP-A-V/3 Egyéb AGR_PIAC_13-1-2013-0008 Egyéb GINOP-2.3.2-15-2016-00043 GINOP
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